CONTEXT: HER2 is a membrane tyrosine kinase and oncogene that is overexpressed and gene amplified in about 20% of breast cancers. When activated it provides the cell with potent proliferative and antiapoptosis signals and it is the major driver of tumor development and progression for this subset of breast cancer. When shown to be overexpressed or amplified by appropriate methods, HER2 is a valuable treatment target. OBJECTIVES: To review the basic biology of the HER2 signaling network, to discuss various approved methods for its detection in clinical specimens, and to describe the impressive results of therapies targeting HER2. DATA SOURCES: Selected literature searchable on PubMed as well as older studies revealed by the literature review were reviewed. CONCLUSION: HER2 is an important member of a complex signaling network and when gene amplified, it results in an aggressive subtype of breast cancer. Patients with tumors found to overexpress HER2 protein or to be amplified for the gene are candidates for therapy that significantly reduces mortality.